Fracture Risk and Psychotropic Medication Use

Although the fracture risk assessment tool, FRAX, is included in numerous clinical guidelines, its algorithm lacks certain clinical factors contributing to fracture risk.

Mental disorders and psychotropic medication use are associated with an increased risk for fracture but are not fully captured by a tool used to assess fracture risk in the general population, according to a study published in JAMA Psychiatry.1

Although the fracture risk assessment tool, FRAX, is included in numerous clinical guidelines, its algorithm lacks certain clinical factors contributing to fracture risk. These include types 1 and 2 diabetes, heart failure, falls, and medications including antihypertensive and psychotropic drugs.

Since psychotropic medications used to treat mental disorders have not previously been examined in the context of FRAX, researchers from the Department of Psychiatry at the University of Manitoba in Winnipeg, Manitoba, Canada, set out to provide the first-ever assessment of FRAX performance in routine clinical practice for men and women with mental disorders and/or using psychotropic medications. They also embarked on determining if these mental disorders and medications contributed to fracture risk beyond the FRAX tool’s estimation.

James Bolton, MD, and colleagues calculated FRAX scores using data on bone density and risk factors collected from 68,730 individuals (62,275 of whom were women and 6455 of whom were men, mean age 64) referred for a baseline dual-energy x-ray absorptiometry scan from January 1996 to March 2013. Data analysis was conducted from November 2013 to October 2016.

The overall rate of mental disorders examined – including anxiety disorders, depression, and schizophrenia – was 18.9% (n = 12,982). Depression was the most common diagnosis at 50.9%. Approximately 17% of individuals took psychotropic medications, and 21% of that group took multiple psychotropic agents.

During a median 6.7 years of follow-up, 8.4% of the study population (5750 individuals) sustained a major osteoporotic fracture and 2.3% (1579 individuals) sustained a hip fracture; 13.1% (8998 individuals) of enrolled participants died.

After adjustment for FRAX score, depression was associated with major osteoporotic fracture and hip fracture, but after adjusting for medication use, these associations were not significant. However, an independent association was noted between the use of psychotropic medication — antipsychotics, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs) — and increased risk of major osteoporotic fracture and hip fracture.

FRAX significantly underestimated the 10-year risk of major osteoporotic fracture by 29% and of hip fracture by 51% for those with depression. FRAX also underestimated the 10-year risk of major osteoporotic fracture for SSRI users by 36%, mood stabilizers by 63%, antipsychotics by 60%, and benzodiazepines by 13%, and underestimated the 10-year risk of hip fracture for SSRI users by 57%, mood stabilizers by 98%, antipsychotics by 171%, and benzodiazepines by 31%. Conversely, FRAX was found to accurately estimate fracture risk in patients without mental disorders and in those not taking psychotropic medications.

“The primary finding is that FRAX significantly underestimated fracture risk among people with mental disorders and among those taking a wide range of psychotropic medications,” the researchers concluded.

“Our results are most applicable to older individuals, especially women, who are considered to be at risk of osteoporosis,” they added. “Health care professionals should be aware of these effects when assessing osteoporosis in people with mental illness.”